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  Meiotic kinetochores fragment into multiple lobes upon cohesin loss in aging eggs.

Zielinska, A., Bellou, E., Sharma, N., Frombach, A. S., Seres, B., Gruhn, J. R., et al. (2019). Meiotic kinetochores fragment into multiple lobes upon cohesin loss in aging eggs. Current Biology, 29(22), 3749-3765. doi:10.1016/j.cub.2019.09.006.

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 Urheber:
Zielinska, A.1, Autor           
Bellou, E.1, Autor           
Sharma, N.1, Autor           
Frombach, A. S.1, Autor           
Seres, B.1, Autor           
Gruhn, J. R., Autor
Blayney, M., Autor
Eckel, H., Autor
Moltrecht, R., Autor
Elder, K., Autor
Hoffmann, E. R., Autor
Schuh, M.1, Autor           
Affiliations:
1Department of Meiosis, MPI for Biophysical Chemistry, Max Planck Society, ou_2205654              

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Schlagwörter: Trim-Away; aging; aneuploidy; centromere; cohesion; human; kinetochore; maternal age effect; meiosis; oocyte
 Zusammenfassung: Chromosome segregation errors during female meiosis are a leading cause of pregnancy loss and human infertility. The segregation of chromosomes is driven by interactions between spindle microtubules and kinetochores. Kinetochores in mammalian oocytes are subjected to special challenges: they need to withstand microtubule pulling forces over multiple hours and are built on centromeric chromatin that in humans is decades old. In meiosis I, sister kinetochores are paired and oriented toward the same spindle pole. It is well established that they progressively separate from each other with advancing female age. However, whether aging also affects the internal architecture of centromeres and kinetochores is currently unclear. Here, we used super-resolution microscopy to study meiotic centromere and kinetochore organization in metaphase-II-arrested eggs from three mammalian species, including humans. We found that centromeric chromatin decompacts with advancing maternal age. Kinetochores built on decompacted centromeres frequently lost their integrity and fragmented into multiple lobes. Fragmentation extended across inner and outer kinetochore regions and affected over 30% of metaphase-II-arrested (MII) kinetochores in aged women and mice, making the lobular architecture a prominent feature of the female meiotic kinetochore. We demonstrate that a partial cohesin loss, as is known to occur in oocytes with advancing maternal age, is sufficient to trigger centromere decompaction and kinetochore fragmentation. Microtubule pulling forces further enhanced the fragmentation and shaped the arrangement of kinetochore lobes. Fragmented kinetochores were frequently abnormally attached to spindle microtubules, suggesting that kinetochore fragmentation could contribute to the maternal age effect in mammalian eggs.

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Sprache(n): eng - English
 Datum: 2019-10-312019-11-18
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1016/j.cub.2019.09.006
 Art des Abschluß: -

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Titel: Current Biology
Genre der Quelle: Zeitschrift
 Urheber:
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Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 29 (22) Artikelnummer: - Start- / Endseite: 3749 - 3765 Identifikator: -